Ammonium Chloride → 2-(6-((1,3-Difluoropropan-2-yloxy)methyl)-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)pyrimidin-4-yl)propan-2-ol

HRID 59178Notes

Reaction equation

[CH3:1][Mg]Br.[F:4][CH2:5][CH:6]([O:9][CH2:10][C:11]1[N:16]=[C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH:28]=[C:27]([CH3:29])[N:26]=[CH:25]3)=[C:20]([O:30][CH3:31])[CH:19]=2)[N:14]=[C:13]([C:32](=[O:34])[CH3:33])[CH:12]=1)[CH2:7][F:8].[Cl-].[NH4+]>C1COCC1>[F:8][CH2:7][CH:6]([O:9][CH2:10][C:11]1[N:16]=[C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH:28]=[C:27]([CH3:29])[N:26]=[CH:25]3)=[C:20]([O:30][CH3:31])[CH:19]=2)[N:14]=[C:13]([C:32]([OH:34])([CH3:1])[CH3:33])[CH:12]=1)[CH2:5][F:4]

Participants

Conditions

Temperature: 0 °C

Procedure

To an ice-cold solution of methylmagnesium bromide (0.71 mL, 1.0 mmol) in THF (6 mL) was added over 5 min a solution of 1-(6-((1,3-difluoropropan-2-yloxy)methyl)-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)pyrimidin-4-yl)ethanone (43 mg, 0.1 mmol) of in THF (3 mL). The reaction was stirred at 0° C. for 30 minutes. Ammonium chloride (sat, aq) was added. The solvent volume was reduced by evaporation. DCM was added and the phases were separated. The organic phase was concentrated and the residue was purified by preparative HPLC to give the title compound as a dry film (34 mg, 76%).

Workup

customThe solvent volume was reduced by evaporation
additionDCM was added
customthe phases were separated
concentrationThe organic phase was concentrated
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-9c97eb42029f4b1694a937c0e94d6c44
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Reaction notes

Loading…